Occupational depigmentation from phenolic and catecholic skin depigmenters (DP) involves a direct attack on melanocytes. The susceptibility of melanocytes to DP may directly stem from physical and chemical interactions of DP with pigment melanin and/or tyrosinase. Binding of DP to melanin would "select" the pigment as a target for chemical attack. Subsequent redox reactions may involve either electron transfer from DP to melanin or "autoxidation" of DP by O2 (probably catalyzed by tyrosinase). These reactions could result in diffusible reactive species capable of causing melanocyte death. To test this hypothesis we propose to (1) measure the binding and redox interactions of selected phenolic and catecholic compounds of widely varying potency with model synthetic melanins, melanin-tyrosinase complexes and with melanoproteins extracted from C-57-BL-6 black mice. The kinetics of the above-mentioned redox reactions will be characterized. Experimental conditions will be chosen which will maximize a given component reaction while minimizing the others. This will allow an approximate separation of the overall interaction into binding, "autoxidation" and electron transfer components. We will use these results as a basis to dissect the total DP-melanosome interaction into simpler components. (2) Induce hair depigmentation by local subcutaneous or intradermal injection of DP into black mice. The relative potencies of the DP's will be estimated visually and by a turbidometric analysis of hair melanin in alkaline-sulfide medium. (3) Seek possible correlation between DP potency and the behavior of one or more component interactions. These results will help in filling the gaps necessary for realizing the following long term goals: (a) early detection and prediction of environmental depigmenters, (b) attainment of a reliable regimen for effecting controlled depigmentation, (c) effective use of the appropriate DP;s as chemotherapeutic agents in malignant melanoma, and (d) determination of mechanistic similarities and differences between occupational depigmentaion and vitiligo.